DESCRIPTION: Breast cancer is the most common malignancy in women in the United States and the second leading cause of death from cancer in American women. The overwhelming majority of patients that die from breast cancer do so due to metastatic spread of the tumor. Despite the use of new chemotherapy agents and antibody-based therapy, the long-term outcome for women with metastatic breast cancer is dismal with less than 2 percent of patients alive 10 years after diagnosis. Thus, new forms of therapy are needed for the treatment of patients with metastatic disease. Immunotherapy is an attractive new option in the treatment of metastatic disease. Response rates of 30 percent have been shown in patients with metastatic melanoma after the infusion of autologous dendritic cells (DCs) designed to stimulate endogenous T lymphocytes. In this project, we have designed a phase I clinical trial based on extensive preclinical in vitro and in vivo work to evaluate the safety and efficacy of giving DCs pulsed with either the wild type epitope from HER-2/Neu, GP2, or an altered epitope generated to improve its immunogenicity, I2L. The trial is a phase I trial in which patients are randomized to receive one of the two peptides pulsed onto autologous DCs. The goals of the trial are to: (1) evaluate the safety of administering three injections of DCs pulsed with either the wild type epitope, GP2, or the altered peptide ligand, I2L, to patients with metastatic breast cancer; (2) measure the clinical and immune response after vaccination and determine whether there is a correlation between a clinical response and the expansion of peptide-specific CTL at the tumor site or in the blood; and (3) determine if the vaccine induces intramolecular or intermolecular epitope spreading and whether this correlates with clinical outcome. The long-term goal of this project is to assess the safety of giving peptide-pulsed DCs to patients with metastatic cancer and to rigorously test the benefits of preclinical protein modeling and the use of animal models to predict the benefits of immune-based therapy.